Safety and immunogenicity of high doses of quadrivalent influenza vaccine in children 6 months through Lee-Jah Chang  1 , Evan J Anderson  2 , Robert Jeanfreau  3 , Ying He  4 , Bryony Hicks  5 , Anju Shrestha  6 , Aseem Pandey  7 , Victoria Landolfi  8 , Iris DeBruijn  9 ; QHD04 Study Group Affiliations Expand Affiliations 1 Sanofi Pasteur, Research and Development, Swiftwater, PA 18370, USA. Electronic address: lee-jah.chang@sanofi.com. 2 Center for Childhood Infections and Vaccines (CCIV) of Children's Healthcare of Atlanta and Emory University Department of Pediatrics, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA. Electronic address: evanderson@emory.edu. 3 MedPharmics, Metairie, LA, USA. Electronic address: robertjeanfreau@medpharmics.com. 4 Sanofi Pasteur, Research and Development, Swiftwater, PA 18370, USA. Electronic address: ying.he@otsuka-us.com. 5 Sanofi Pasteur, Research and Development, Swiftwater, PA 18370, USA. Electronic address: bryony.hicks@sanofi.com. 6 Sanofi Pasteur, Global Pharmacovigilance, Swiftwater, PA 18370, USA. Electronic address: anju.Shrestha@sanofi.com. 7 Sanofi Pasteur, Research and Development, Swiftwater, PA 18370, USA. Electronic address: aseem.Pandey@sanofi.com. 8 Sanofi Pasteur, Research and Development, Swiftwater, PA 18370, USA. Electronic address: victoria.landolfi@sanofi.com. 9 Sanofi Pasteur, Research and Development, Marcy L'Etoile, France. Electronic address: iris.debruijn@sanofi.com. PMID: 33610374 DOI: 10.1016/j.vaccine.2021.02.014 Free article Item in Clipboard

Abstract

Quadrivalent high-dose inactivated influenza vaccine (Fluzone® High-Dose Quadrivalent, IIV4-HD) was licensed in the USA in 2019 for adults ≥ 65 years of age. This Phase II study examined safety and immunogenicity of 3 dose formulations of IIV4-HD in healthy children. In a randomized, modified double-blind, active-controlled trial in the USA and Canada, 661 children aged 6 months through < 18 years received 1 or 2 doses intramuscularly of standard-dose quadrivalent influenza vaccine (IIV4-SD; 15 µg HA/strain), IIV4-HD at 3 dose levels (30, 45, and 60 µg HA/strain), or adjuvanted trivalent influenza vaccine (aIIV3, 7.5 µg HA/strain). Rates of unsolicited AEs were similar irrespective of dose. No treatment-related serious adverse events or deaths were reported. Reactogenicity was slightly higher for IIV4-HD than IIV4-SD, although most solicited reactions were grade 1 or 2. Hemagglutination inhibition (HAI) and seroneutralization antibody titers were measured 28-35 days after each dose. Geometric mean HAI titers increased with increasing hemagglutinin dose, especially in children 6 months through < 3 years. For IIV4-HD 60 µg, in participants 6 months through < 18 years of age, the geometric mean titer ratio (95% confidence interval) versus IIV4-SD was 1.35 (0.94, 1.94) for A/H1N1, 2.51 (1.77, 3.55) for A/H3N2, 1.60 (1.17, 2.18) for B/Victoria, and 1.51 (1.13, 2.03) for B/Yamagata. The GMT ratio (95% confidence interval) for IIV4-HD 60 µg versus IIV4-SD was highest for participants 6 months through < 3 years of age: 4.24 (2.05, 8.76) for A/H1N1, 3.14 (1.53, 6.44) for A/H3N2, 2.04 (1.10, 3.77) for B/Victoria, and 1.92 (1.08, 3.41) for B/Yamagata; similarly, seroneutralization antibody GMT ratio was highest in these participants: 170 (84.6, 340) for A/H1N1, 7.13 (4.90, 10.4) for A/H3N2, 35.8 (22.1, 58.1) for B/Victoria, and 22.7 (14.7, 35.0) for B/Yamagata. This study showed that IIV4-HD (60 µg HA/strain) provides improved immunogenicity without affecting vaccine safety in children.

Keywords: High-dose; IIV4-HD; Immunogenicity; Influenza vaccination; Pediatric; Safety.

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